Abstract
Nicotine (NE), a principal alkaloid in tobacco, functions as both a neurotoxin and a candidate for therapeutic applications. This research explores the tripartite interactions among the host organism, its endosymbiotic microbiota, and the toxicant agent, utilizing Drosophila melanogaster and its native symbiont Wolbachia (wMel Pop strain). To elucidate the mechanisms governing host-microbe-toxicant dynamics, the influence of nicotine on the developmental biology of Drosophila was assessed through dietary administration to two strains: wMel Pop-infected and uninfected Drosophila (Dmel T). Additionally, the impact of nicotine on Drosophila ontogeny and the regulatory role of Wolbachia were examined employing integrated dual transcriptomic and metabolomic analyses. This multi-omics approach demonstrated that Wolbachia infection modulates the host’s transcriptional and metabolic profiles, consequently influencing its response to nicotine exposure. The findings emphasize the critical influence of host-associated microbiota in modulating toxicokinetic pathways in Drosophila. The online version contains supplementary material available at 10.1186/s12864-025-12503-y.
